2023 CSACI annual scientific meeting book of abstracts

Background: Occupational asthma accounts for nearly 18% of cases of adult-onset asthma, but prevalence rates vary between men and women. This may be due to sex distributions in industries and occupations associated with developing occupational asthma. The purpose of our study was to assess sex differences in occupational and clinical characteristics of patients with occupational

Background: Mucus plugging contributes to asthma severity and is often overlooked in clinical practice [1].We recently reported IgG autoantibodies in sputum, and they contribute to asthma severity [2].We hypothesize that rheological properties of mucus can be affected by autoantibody-triggered eosinophil extracellular traps (EET) that reduce its clearance potential leading to persistent plugging evident on chest Computed Tomography (CT).Methods: Sputum samples from asthma patients with available chest CT radiology reports (n = 102, conducted clinically within 3 months) were examined for antinuclear antibodies (ANA) (HUMAN Diagnostics, [2]).Evidence of mucus was subjectively quantified based on the radiology report as significant, moderate, mild or none.Rheological properties of expectorated sputum (n = 15) were assessed using Rheomuco ® rheometer (Rheonova, Gières, France).Effects of EETs on mucus rheology were assessed ex-vivo by adding increasing numbers (2.5-5 × 10 6 ) of EETosing eosinophils (induced by autoantibodies) to expectorated sputum samples.Finally, 21-day old Calu-3 airway liquid interface (ALI) epithelial layers exposed to EETs for 48 h were examined for secreted mucin proteins (MUAC5 and MUC5B) (Novus Biologicals ELISA Kit).Results: Patients with evidence of mucus plugging on CT had significantly higher sputum ANAs (p = 0.01).Sputum samples from patients with "significant" mucus plugging on CT had increased rheology parameters of critical stress, elastic modulus, and viscous modulus compared to those who had none/less (p < 0.05).Eosinophils (2.5 × 10 6 ) derived from healthy donors (n = 3) were stimulated with autoantibodies to trigger EETosis in-vitro.EEETs increased the critical stress and viscosity of sputum.Finally, presence of EETs increased the release of MUCAC5 from ALI epithelial layers causing 1.65-fold increase in MUC5AC:MUC5B ratio compared to untreated wells (n = 2).

Conclusions:
The study provides proof-of-concept evidence that sputum rheology can be affected by the presence of autoantibodies in an eosinophilic airway that leads to extracellular trap release and subsequent mucus production and plugging.
Background: Compared to families not managing food allergy, families managing food allergy face higher food costs and thus may be at higher risk for food insecurity.Our scoping review aims to examine the prevalence of food insecurity within families managing food allergy with consideration to demographic factors and how food insecurity is operationalized.Methods: The current scoping review follows Arksey and O'Malley's framework, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews review guidelines and uses search terms developed by a health sciences librarian.Databases searched included MedLine, EmBase, Scopus, and Food Sciences and Technology Abstracts as well as the grey literature.Original articles, regardless of date of publication, focused on food allergy and food insecurity, published in English or French, were eligible for review.All articles will be screened by two reviewers blinded to each other's initial decisions.Disagreements between reviewers will be resolved through discussion or by a third reviewer if consensus cannot be reached.Results: Peer-reviewed literature was searched on June 20, 2023, yielding 3748 unique articles.We are currently in the process of searching the grey literature.Afterwards, all articles will be screened.Once the final sample of articles is established, we will extract data from each article pertaining to the definition of food insecurity used, rates of food insecurity, and the influence of demographic factors.This information will ultimately be synthesized using a narrative synthesis.Conclusions: Families affected by food allergy may face an elevated risk of experiencing food insecurity.Estimating the rates of food insecurity among families navigating food allergy will help identify potential discrepancies in food insecurity between families with and without food allergy while contributing to further policy guidance.Thank you to Carol Cooke of the University of Manitoba Neil John Maclean Health Sciences Library for guidance in developing search terms.
Background: Nurse Educators at the Children's Allergy & Asthma Education Centre (CAAEC) have monitored asthma-related health care use at the Children's Hospital of Winnipeg before and during the COVID-19 Pandemic, particularly the yearly September epidemic of asthma exacerbations.Methods: As part of ongoing monitoring of health care use, Shared Health provided statistics regarding Children's Hospital Emergency Department (ED) visits and hospitalizations for asthma from 2019-2023.Comparisons between 2019 and 2020-2023 were made for ED visits for asthma, hospitalizations for asthma, and asthma admissions to the Pediatric Intensive Care Unit (PICU) directly from the ED or as transfers from the ward.We also noted dates of changes in public health measures from 2019-2023.Results: Compared with ED visits for asthma in September 2019 (n = 180), we observed a 79% decrease in September 2020 (n = 38), when public health measures were most restrictive, a 39% decrease in September 2021 (n = 110), when mask mandates remained in effect in schools, and a 67% increase in September 2022 (n = 300) when most public health restrictions were removed.Compared with hospitalizations for asthma in September 2019 (n = 3), we observed no change in 2020 (n = 3), a 300% increase in 2021 (n = 12), and a 1100% increase in 2022 (n = 36).In 2022 versus 2019, PICU asthma admissions directly from the ED increased by 175% and from the ward increased by 263%.The increases in ED visits and hospitalizations for asthma began in April 2022 and persisted until December 2022.Conclusions: The Children's Hospital of Winnipeg saw a dramatic increase in ED visits and hospitalizations for asthma in 2022, peaking in September.Yearly changes in the September epidemic during the Pandemic coincided with changes in public health restrictions.The dramatic increase in hospitalizations and PICU admissions in 2022 demonstrated increased severity and frequency of asthma exacerbations after the lifting of public health measures.

Food allergy/anaphylaxis 16
Real world experience: a retrospective pediatric chart review to determine why patients discontinue oral immunotherapy Amy Plessis 4 , Scott B. Cameron 1,2,3 , Victoria E. Cook 1,2,3 1 Division of Allergy and Immunology, Department of Pediatrics, University of British Columbia, Vancouver, BC; 2 British Columbia Children's Hospital Research Institute and the University of British Columbia, Vancouver, BC; 3 Community Allergy Clinic, Victoria, BC; 4  Background: Oral immunotherapy (OIT) is an increasingly prevalent management strategy for IgE-mediated food allergy.Despite promising results with OIT there is still a lack of information surrounding reasons for discontinuation of OIT.The primary reason stated in the literature for discontinuation is adverse gastrointestinal effects.Social factors contributing to OIT discontinuation have not been well reported.We hypothesize that for many families, the social considerations are significant contributors to discontinuation.Methods: We report a retrospective chart review of 50 patients in community pediatric allergy practices who discontinued OIT between October 1 2017-October 27 2022.The reasons for discontinuation were identified and classified into five main categories: unsafe choices, anxiety, adverse effects of OIT, uncontrolled comorbidity and social factors.Categories were not exclusive.Results: Data were available on 50 patients, aged 10 months to 18 years and 2 months.Overall rate of discontinuation was 9.8% of which 40 patients (82%) discontinued during buildup phase and 9 patients (18%) discontinued during maintenance.30 patients (60%) had multiple reasons for discontinuing OIT.The most common reason for discontinuation was social factors, which were identified in 29 patients (58%).22 patients (44%) discontinued OIT due to adverse effects, gastrointestinal symptoms being the most prevalent.13 patients (26%) were identified as having anaphylaxis contribute to discontinuation and 17 patients (34%) had anxiety leading to discontinuation.Conclusions: Our data highlights the importance that social factors and anxiety play in the success of OIT completion which to the best of our knowledge is underrepresented in the current literature.Our data supports that when selecting patients who are good candidates for OIT we need to consider not only the patient's medical history, but also their social history and support networks to optimize the successful completion of OIT.
Background: Food allergy affects close to 500,000 individuals in Canada [1].Globally, the number of individuals with food allergy has continued to rise with no cure for those whose allergies are lifethreatening [2].There is much published knowledge about how teenaged children feel about their life-threatening food allergies with reports of bullying, feeling excluded or like a burden to others (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).Far less is known about mothers' experiences with caring for a teenaged child with anaphylactic food allergies.It is known that mothers report worries about life transitions, carrying of epinephrine auto-injectors, peer pressure, and avoidance of the offending allergen, to name a few (23)(24)(25)(26)(27). Methods: In this qualitative philosophical hermeneutic inquiry study, mothers were interviewed about this experience as their children were now teenagers who lived with life-threatening food allergies.This exploration uncovered new understandings about this experience that have not previously been published.Influenced by the philosophical hermeneutics of Hans-Georg Gadamer; transcription of interviews, in-depth engagement with the transcriptions, and analysis of interviews in hermeneutic research tradition occurred (28).Results: Findings revealed that this experience encompasses vigilance, watchfulness, and surveillance, advocacy, looking toward the future while looking backwards over life already lived, and allergies taking a backseat to other worries during the teenaged years.Conclusions: Vigilance, watchfulness, and surveillance are a strong component of the experience of mothers of teenagers with life-threatening food allergies, but allergies do take a backseat to other worries as the teenager grows.Recommendations are offered on how nurses and other healthcare professionals, and mothers with experience themselves, can support and provide hope for families with individuals with newly diagnosed anaphylactic food allergies.

Background:
We previously described the safety of preschool tree nut oral immunotherapy (TN-OIT) and both the safety and effectiveness of preschool peanut oral immunotherapy (P-OIT) in a real-world setting.We sought to determine the effectiveness of preschool TN-OIT after at least one year of daily maintenance TN-OIT.Methods: As part of a Canada-wide quality improvement project, preschool-age children with (1) an objective reaction to tree nut and a positive skin prick test or specific IgE level of 0.35 kU/L or greater or (2) specific IgE level of 5kU/L or greater received a follow-up OFC to cumulative 4000 mg tree nut protein after at least one year of 300 mg maintenance TN-OIT.Each patient completed TN-OIT and follow-up OFC to at least one tree nut (cashew/pistachio, walnut/pecan, hazelnut, almond, or macadamia nut), with some patients completing TN-OIT to more than one tree nut simultaneously, with follow-up OFCs for each.Effectiveness of desensitization was defined as proportion of patients with negative follow-up OFC.Symptoms were classified using the modified World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System (1, mildest; 5, fatal).Results: 47 patients completed TN-OIT to at least one tree nut and subsequently underwent 54 follow-up OFCs; 45/54 (83.3%) had a successful OFC to 4000 mg protein and 53/54 (98.1%) tolerated a cumulative dose of greater than or equal to 1000 mg protein.Of the 9 reactions, 6 (66.7%) were grade 1 reactions and 3 (33.3%)were grade 2 reactions, with no grade 3-5 reactions.All grade 2 reactions were to cashew.No patients required epinephrine during the follow-up OFC.Conclusions: Our preliminary data demonstrate that real-world preschool TN-OIT is effective, with comparable outcomes to previously published P-OIT data.For those who reacted, the vast majority had their threshold increased sufficiently to protect against accidental exposures.TN-OIT should be considered for preschoolage children as an alternative to strict avoidance.
Background: Oral immunotherapy (OIT) has emerged as a promising approach.However, concerns regarding safety and the lack of standardized protocols have impeded the widespread adoption of OIT.Methods: This study aims to address the gaps related to OIT for milk and peanut protocols by focusing on developing safer yet effective protocols.Group A followed the standard protocol with a dose of 200 ml of milk and 300 mg of peanuts.Group B employed lower target doses of 50 ml milk and 30 mg peanuts.Group C incorporated processed forms of the allergens, such as daily baked goods with milk and peanut snacks.The participants were recruited from allergy clinics at the Montreal Children's Hospital.Allergic reactions were classified as mild allergic reaction (AR), moderate AR; severe AR, anaphylactic allergic reaction (AAR); severe AAR.Anaphylaxis was defined by involving at least two organ systems/hypotension [1].The severe anaphylactic reaction was defined by cyanosis, hypoxia, respiratory arrest, hypotension, dysrhythmia, confusion, or loss of consciousness.Results: There were 16 children recruited for milk and 16 for peanuts in each group A, B, and C. The median age was 7.5 years (IQR: 3.75).Among children undergoing peanut OIT, 6 had AR, and 6 had AAR.Among children undergoing milk OIT, 10 had AR, and 10 had AAR.For milk, OIT use of a protocol with baked goods was associated with a lower risk of severe allergic reactions (aOR, 7.76; CI, 1.33-45.26).The male sex (8 males) was associated with less moderate/ severe anaphylactic reactions (aOR, 0.08; CI, 0.01-0.87).

Conclusions:
Baked milk may offer a safer strategy for OIT.However, the limited sample size precludes definitive conclusions, and its relative efficacy needs to be studied.Further research with larger sample sizes is necessary to compare appropriately between the three protocols.Background: Peanut oral immunotherapy (OIT) lowers the risk of allergic reactions by gradually exposing allergic individuals to increasing amounts of peanuts until a maintenance dose of 300 mg is reached.However, this process is hindered by frequent dose-related adverse reactions, which often result in participant withdrawals.Data on immunologic parameters linked to maintenance doses below 300 mg are limited.Methods: A subset of 29 peanut-allergic children aged 3 to 18 years from a broader peanut OIT trial of low 30 mg (N = 13) vs standardmaintenance dose 300 mg (N = 16) was evaluated.Serum samples were analyzed at two timepoints: before and after one year of dose escalation.Total peanut-and Ara h2-specific immunoglobulin (Ig) G4 and IgE levels were obtained via ELISA.

Results:
The median participant ages were: 30 mg group-14 years (53% males), 300 mg group-13.5 years (37.5% males).There were no significant differences between groups for both peanut-specific-IgG4 and IgE levels at baseline.After a median escalation phase of 16 Background: Peanut oral immunotherapy (OIT) is commonly achieved using crushed raw or roasted peanut, although adverse reactions throughout treatment are frequent.Alternative thermal processing methods and their effects on peanut protein allergens have been explored in recent years.High-pressure and temperature autoclaving has been shown to alter overall protein secondary structure and decrease in vitro binding of peanut-specific immunoglobulin E (sIgE) in sera from peanut-allergic patients.However, data assessing clinical responses to the autoclaved peanut are lacking.Methods: Forty-one peanut-allergic individuals were recruited to the Montreal Children's Hospital for skin prick testing (SPT) using standard commercial peanut extract and an extract created from autoclaved peanuts (130 °C, 30 min) both adjusted to equal protein concentrations.The median age was 20 years old, and 17 subjects were female.Wheal diameters were recorded, and serum samples were obtained to compare peanut-sIgE levels via ELISA.Group comparisons were done using the Wilcoxon signed-rank test.

Results:
The SPT results showed a significant decrease in wheal diameter in peanut-allergic subjects using the autoclaved peanut extract (mean ± SD = 6.1 ± 5.5 mm) when compared to the commercial standard (11.3 ± 6.4 mm; p < 0.001).Upon stratifying the participants into two groups, one that experienced smaller wheal sizes when using the autoclaved peanut extract (≥ 3 mm less; N = 30) and another with no significant decrease (N = 11), those with smaller wheal sizes to the autoclaved extract demonstrated significantly lower sIgE levels to total peanut (p = 0.029) and allergen components Ara h 1 (p = 0.015), Ara h 2 (p = 0.007), and Ara h 8 (p = 0.017).Conclusions: Altogether, the observed decreases in SPT wheal sizes and sIgE binding levels with the autoclaved peanut suggest that autoclaving decreases allergenicity, making it a potential improved substrate for peanut OIT.Further clinical studies are ongoing to assess the level of safety of the autoclaved peanut in allergic individuals.Background: Anaphylaxis is a potentially life-threatening reaction.It is often triggered by the ingestion of a food allergen or sting from a venomous insect [1].The current definition of anaphylaxis varies but the guiding principle includes the onset of symptoms in two or more organs within minutes to several hours of exposure to the allergen [2].Presence of hypotension increases the likelihood that the presentation was a severe systemic reaction [3].However, there is some data that supports the presence of hypertension immediately after exposure to an allergen as a clinical finding; driven by possibly a compensatory vasopressor response.Therefore, this study looks at redefining the definition of anaphylaxis by studying the vitals of patients who present with anaphylaxis.
Methods: This is a retrospective cohort study on patients that have visited London Health Sciences Center (LHSC) emergency department between 2012-2022.Using the LHSC electronic medical records, the vitals of patients with a diagnosis of anaphylaxis will be reviewed for hypertension.Hypertension is defined as a systolic blood pressure above 140 [4].REB approval was obtained from Western University prior to the initiation of this study.Results: Preliminary data has been collected on 664 patients.Within this data set, 34% of the patients had a systolic blood pressure greater than 140 at time of triage while 3% were hypotensive with a systolic less than 90.138 females presented to the emergency department while 86 were male and the average was 43.8 years old.Within the 224 patients, 12 were admitted to hospital for further monitoring, 1 patient died, with 7 patients leaving after initial treatment and 204 patients formally discharged.Conclusions: Although a proportion of patients presented to the triage with blood pressures in the normal range, there is still a significant number of anaphylactic patients who present to the emergency department with hypertension.
Background: Sesame and sesame-containing foods have become increasingly prevalent in Western diet, meaning that patients allergic to sesame are at risk for severe, life-threatening reactions.We aimed to assess the efficacy and safety of a modified sesame desensitization protocol in children in real-world clinical practice.Methods: Children with a history of sesame allergy and a positive skin prick test to sesame were recruited at the Montreal Children's Hospital and the Children's Clinic located in Montreal.After obtaining consent, an initial dose of sesame protein (3-25 mg) was introduced in the form of either tahini muffin or sesame seeds.Patients continued the same dose for 2-5 weeks at home, filled out a symptom diary, and returned to the clinic for updosing until maintenance was reached (2 teaspoons of hummus or 2 mL of tahini).A proportional odds logistic regression model was used, controlling for age and sex, to determine the difference in the severity of allergic reactions between the tahini muffin and sesame seed groups.Results: Between January 2021 and May 2023, 59 children (57% male; median age 2.4 years) were recruited.The majority of patients (74%) had eczema and 18% had asthma.Oral desensitization was performed using one of two strategies according to the allergist: initial doses were either tahini muffin (59%) or sesame seeds (41%).To date, 10 patients (17%) reached the maintenance dose.Ten patients (17%) experienced a non-anaphylactic reaction, and 6 patients (10%) experienced an anaphylactic reaction.The probability of a severe reaction, such as anaphylaxis, was four times higher in the sesame seeds group compared to the tahini muffin group, with an odds ratio (95% CI) of 4.1 (1.1-14.9).Conclusions: Modified sesame desensitization protocols may be safely used in children with sesame allergy.

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Retrospective review of predictors of peanut allergy at a Canadian allergy and immunology clinic Mary Wang 2 , Joella Ho 1 , Harold Kim 3,4  Background: Peanut allergy is one of the most common types of food allergy.Identifying predictors for peanut allergy can help in understanding its pathogenesis and detecting individuals at risk before a life-threatening reaction occurs.Our study aimed to identify predictors of peanut allergy from a patient's clinical history and commonly used investigations.Methods: A retrospective chart review was conducted on 451 patients referred for food allergy assessment at a Canadian hospital-based allergy and immunology clinic between January 2015 and May 2021.Patients who were investigated for peanut allergy were selected for further analysis.Peanut allergy diagnosis was established through unsuccessful oral food challenges or clinical judgment.Simple logistic regression was used to determine the variables predicting peanut allergy, and multiple logistic regression was then used to develop a peanut allergy prediction model with the variables identified.Results: Among the 451 patients investigated for food allergy, 68.0% presented with concerns of peanut allergy.Among these patients, 70.5% were diagnosed with peanut allergy.The age range of patients varied from 8 months to 67 years.The following variables were identified as predictors of peanut allergy: male sex (odds ratio(OR) = 2.28, 95% confidence interval (CI) = 1.38, 3.78), asthma (OR = 2.20, 95%CI = 1.27, 3.90), age at index reaction (OR = 0.94, 95%CI = 0.88, 0.98), skin-prick test wheal size (OR = 1.23, 95%CI = 1.14, 1.34), and Arah2 IgE titres (OR = 1.02, 95%CI = 1.01, 1.03).These variables were used to develop a prediction model for peanut allergy, with 91.59% positive predictive power and 68.57% negative predictive power.Conclusions: A predictive model integrating sex, presence of asthma, age of index reaction, skin-prick wheal size, and Arah2 IgE titres may facilitate safe diagnosis of peanut allergy.Notably, the negative predictive power of this model remains low.Further research should focus on validating this model using a larger cohort and investigating factors that reduce the likelihood of peanut allergy.

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Allergy-friendly food subsidy perceived to reduce burden on families managing food allergy Zoe Harbottle 1,2,3 , Michael A. Golding 2,3 , Manvir Bhamra 1,2,3 , Moshe Ben-Shoshan 4 , Jennifer Gerdts 5 , Elissa M. Abrams 2,3 , Sara J. Penner 6 , Jo-Anne St-Vincent 7 , Jennifer L. Protudjer Background: There is a substantial burden placed on families managing food allergy due to the additional effort required and the disproportionate costs of allergy-friendly food products.With the recent increases in food prices, the impact of this burden is further exacerbated.In this study, we aimed to qualitatively evaluate a milk allergy-friendly subsidy program for lower-and middle-income families in Winnipeg, Canada.Methods: As part of an overarching mixed-methods intervention, families living or working within Winnipeg with an annual net household income of ≤ $70,000 in the year prior to recruitment and a child age < 6 years with a physician diagnosed milk allergy were recruited from a database maintained by the principal investigator, social media, and word-of-mouth.From March-August 2022, participating families received bi-weekly deliveries of subsidy kits containing ~ $50 worth of milk allergy-friendly foods.End-of-study semi-structured interviews were conducted with participants to better understand their thoughts on the program.Each interview was audiorecorded, transcribed verbatim, and analyzed thematically.Results: Eight interviews were completed.On average, parents were 29.88 ± 4.39 years old and children were 2.06 ± 1.32 years old.In addition to physician-diagnosed cow's milk allergy, other food allergies included peanut and egg (each n = 4).We identified three themes: food allergy poses a substantial burden on families, parents prioritize their child's dietary needs before their own needs, and families perceived this allergy-friendly food subsidy to have emotional and financial benefits.Conclusions: This subsidy was perceived to positively impact families' food costs and stress.Not only does this demonstrate the need for help for families managing food allergy but also, provides valuable information to inform the development of programs focused on alleviating the burden of food allergy.Future programs should strive to incorporate a greater variety of foods to further the benefits obtained.

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Engaging with experts as part of the evolving conversation on the treatment of anaphylaxis Laura May Miles 1 , Jennifer L. Protudjer 2,3,4  Background: Prompt epinephrine use is the first-line treatment for anaphylaxis.Through engagement via a webinar hosted by Food Allergy Canada, we aimed to assess the level of comfort and knowledge surrounding epinephrine autoinjector (EAI) use.Methods: In May 2023, an immunologist and allergy researcher delivered a webinar titled "Epinephrine, Benadryl ® , and the evolving conversation on the treatment of anaphylaxis." Attendees were polled before and after the webinar.Results: The 132 attendees included: 29% (38) legal guardians of a child with a food allergy, 22% (29) health care professionals, 14% (19) adults with a food allergy, 11% (14) dieticians, 11% (14) individuals interested in food allergies, 8% (11) researchers/educators, and 2% (3) caregivers; data were missing for 3% (4).A total of 76 and 73 responses were recorded before and after the presentation, respectively.There was an overall 80% increase in individuals who reported feeling "very comfortable" in EAI use.Top knowledge concerns were uncertainty of reaction severity (76%), lack of confidence in recognizing when to use (52%), and the need to present to the hospital following EAI use (33%).Among responders, 41% reported that, if given guidance on the "wait and see" approach, they would be more likely to use EAI.Conclusions: Expert-led information sessions to patients, caregivers and other health professionals may support improved comfort in EAI use to treat anaphylaxis and contribute to identifying gaps in knowledge of anaphylaxis management.Background: Atopic dermatitis (AD), food allergy, and asthma are common pediatric conditions, which are negatively associated with health-related quality of life.Previous research has primarily focused on the association between asthma and parent-child relationships, leaving uncertainty regarding the consequences of AD and food allergy on this relationship.We aimed to conduct a scoping review of the literature examining associations between allergic disease and parent-child relationships.Methods: We conducted a scoping review, informed through consultation with a health sciences librarian.Articles involving the quality of parent-child relationships amongst children (< 18 years) with AD, food allergy, or asthma were included.Searches were conducted in the MEDLINE, PsycInfo, and Scopus databases, and limited to original research published in English, French, or Spanish.After the initial search, two co-authors independently screened studies against the inclusion criteria.A secondary search was completed to identify eligible articles.We identified common themes between the included articles, by specific condition and cross-conditions.As findings for asthma were different than AD and food allergy, we compared asthma with the latter two conditions.Results: In total, 860 articles were identified, of which 28 articles (3.3%) were included.Parents of children with asthma exhibited more overprotective/intrusive parenting styles compared to parents of healthy children, as indicated by common themes across included articles.Although inconsistent, some studies also observed higher levels of critical attitudes among parents of children with asthma, and lower levels of attachment security among their children.There were no eligible studies addressed the relationship between food allergy and parent-child attachment, while three studies explored the relationship between AD and parent-child relationship quality, for which the results were mixed.Conclusions: Asthma seemingly contributes to more overprotective/ intrusive parenting styles, and potentially decreased attachment security amongst children with vs. without allergic conditions.Corresponding studies for AD and food allergy are limited.Background: Reactivity thresholds can help assess risk from allergenic foods and provide critical information for the management of food allergy [1].However, there is an unmet need to identify predictors of reaction thresholds as they currently have not been estimated with certainty and vary significantly per individual [1,2].Two Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trials, EPITOPE and PEPITES, were designed to evaluate the safety and efficacy of a peanut patch containing 250 µg peanut protein (VP250) for 12 months in children aged 1 through 3 years and 4 through 11 years, respectively [3,4].These studies provided an extensive database of double-blind, placebo-controlled food challenges (DBPCFC) to understand the relationship between baseline factors, such as age and IgE levels, and reaction thresholds.Methods: DBPCFCs were performed per PRACTALL guidelines at entry in peanut-allergic children.Oral food challenges (OFC) were discontinued when symptoms met prespecified stopping criteria.A linear regression analysis was performed to assess the relationship between eliciting dose (ED) and baseline age and sIgE in all children screened in the EPITOPE and PEPITES studies.Results: In combination, 769 children were randomized.The last ingested dose and baseline ED were negatively correlated with age, sIgE (P < 0.0001), and Ara h2 sIgE (P < 0.0001).Conclusions: In this analysis of a large database of DBPCFC's to peanut, age and sIgE are negatively correlated with baseline ED.Consistent with other studies, high sIgE here is associated with a lower ED [5], while age is positively correlated with sIgE [6].Just as food allergy prevention and treatment studies suggest increased plasticity of the allergic immune system and greater success rates at younger ages, these data may suggest an increased benefit to initiating peanut allergy treatment early after diagnosis.Background: Egg Oral Immunotherapy (OIT) has become a treatment option to desensitize individuals allergic to hen's egg.Though promising, better understanding of efficacy and safety of egg OIT is needed.Methods: Participants with egg allergy were confirmed by oral food challenges.Twenty-six underwent OIT at the Montreal Children's Hospital.During dose escalation, graded doses were given in-clinic followed by at-home dosing as instructed until the target dose of 300 mg egg protein was reached.Adverse reactions were recorded following each dosing if present and their severity graded.Anaphylaxis was determined according to clinical criteria by Sampson et al. 2006.Risk factors associated with anaphylaxis were examined via Poisson regression.Results: Among 26 participants eligible for egg OIT, 58% were females and mean age was 12.2 years.Apart from 9 in progress and one withdrawn, 15 out of 16 (93.8%)participants reached 300 mg, including 6 crossed over following one-year observation.The threshold doses in these 6 participants were comparable before and after the observation (Wilcoxon test, p = 0.1).During dose escalation, a total of 6859 doses were taken, and 1190 episodes of adverse reactions were recorded, in which 53.7% involved the gastro-intestinal system 21.2% involved the mucocutaneous system, and 8.9% involved the respiratory system.Organ systems affected varied widely by individuals.The three most common complaints were abdominal discomfort, oral pruritus and nausea.In total, 1.5% (18/1190) episodes of adverse reactions were anaphylaxis.Factors (Incidence rate ratios, Confidence Interval) significantly associated with anaphylaxis included Male (3.59, 1.37-10.56,p = 0.013), eczema (0.32, 0.11-0.84,p = 0.025), as well as cumulative dose [log] (0.63, 0.46-0.83,p = 0.002) and wheal size of skin prick test (0.84, 0.73-0.95,p = 0.01).Conclusions: Egg OIT is effective with high success rate of desensitization and low incidence of severe adverse reactions.Background: Cow's milk allergy, caused by ingestion of proteins such as casein, is one of the leading causes of anaphylaxis in children.Mouse models that mimic symptoms of anaphylaxis in humans are needed to evaluate potential new therapies for food allergy.According to the atopic march, severe eczema is associated with food allergy in children and may be the portal of sensitization.Therefore, we established a mouse model in which the mice are transdermally sensitized.Methods: Six-to eight-week-old male and female C57BL/6 mice (n = 3-5) were exposed via gently abraded skin to dissolved casein or PBS weekly for six weeks.Two weeks after the last sensitization, all mice were challenged intragastrically with 50 mg of dissolved milk powder.The challenged mice were observed with live and infrared cameras to assess clinical symptoms and skin surface temperature.Following sacrifice, tissue samples including spleen, inguinal lymph nodes, and axillary lymph nodes were assessed.We also compared transdermal and subcutaneous sensitizations to determine the more effective route of eliciting anaphylactic reactions in mice.Results: Following casein sensitization, we detected casein-specific IgE in all sensitized female mice which peaked on day 28.IgE+ B cells were significantly increased in the inguinal lymph nodes of sensitized female mice compared to controls.We also observed signs of moderate anaphylactic reactions including continuous scratching and decreased reactivity in the female casein-sensitized mice.We were unable to detect an increase in casein-specific IgE in subcutaneously sensitized mice.Conclusions: These findings suggest that four weekly transdermal sensitizations were sufficient to induce systemic reactions in intragastrically challenged female C57BL/6 mice.This mouse model can serve as a preclinical model to determine the efficacy of potential treatments for food allergy.population, with fatalities rare but reported.Detailed data of fatal anaphylaxis in Canada are scarce.We aimed to assess cases of anaphylaxis fatality in Canada, between January 2020 and June 2023, and identify risk factors.Methods: The CRAFT: Canadian Registry for Anaphylaxis Fatalities includes data, from January 2020 onward, on fatal anaphylaxis, obtained from social media, professional associations, patient organizations (Food Allergy Canada, Canadian Anaphylaxis Initiative) and through coroners' reports.Anaphylaxis was operationalised as coroner-reported cases of fatal anaphylaxis, even if the history was not consistent with National Institute of Allergy and Infectious Disease (NIAID) definition of anaphylaxis, namely involvement of at least two organ systems/hypotension [1].Probable anaphylaxis was operationalised as a history consistent with this NIAID definition.Results: Between January 2020 and June 2023, 10 cases of fatal anaphylaxis were identified.The male to female ratio was 1:1, five were adults, and five were defined as probable anaphylaxis.Suspected triggers included food (3/10; including one case of each: milk, peanut, and pine nut), drugs (3/10; including one case each of Septra, amoxicillin, iodine contrast media), insect allergy (1/10; wasp), dog hair (1/10), and unknown (1/10).Reported comorbidity included asthma (5/10) and heart disease (2/10).About half (5/9) received pre-hospital epinephrine.Timing of epinephrine administration was available for four cases (one was after five minutes, one after 15 min, one after 1 h [as an inpatient], and one after few hours).Conclusions: Consistent with data from other countries, food and drug were the main triggers of fatal anaphylaxis, as was the delayed use of epinephrine.Asthma was a common comorbidity.Continued patient-and population-level education regarding allergen avoidance, and the prompt use of epinephrine are needed.

Predominant cofactors for epinephrine administration during preschool oral immunotherapy
Alexandra Baaske Background: Dupilumab inhibits the shared interleukin (IL)-4/IL-13 receptor, IL-4Rα, and rapidly improves sense of smell and healthrelated quality of life in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).In mice, administration of IL-4, but not IL-13, induces smell loss by Day 5, suggesting that IL-4-signaling effects play a dominant role in the restoration of smell.This study investigated the pathophysiological mechanisms of IL-4-evoked loss of smell in mice using transcriptomic and proteomic profiling.Methods: Male BALB/cJ mice received intranasal administration of IL-4 and/or IL-13 daily for 5 days (Days 0-4).IL-4Rα antibody (dupilumab surrogate) was injected intraperitoneally on Days -3, 0, and 3.After treatments, the olfactory epithelium was dissected and subjected to RNA extraction for transcriptomic profiling and protein extraction for proteomic analysis.Gene set enrichment analysis (GSEA) was used to identify regulated functional pathways.
Results: In transcriptome analysis, IL-4, but not IL-13, upregulated genes involved in olfactory signaling (pim3, crem, creb3L1), calcium signaling (clca3b, ryr1), neuronal regeneration (ngfr, dlx3, nr4a1), and immune response (ccl8, cd163, Ly6d).In addition, IL-4, but not IL-13, downregulated genes encoding olfactory receptors (olfrs).GSEA indicated significant effects of IL-4, but not IL-13, on gene module scores for neuroimmune interactions and synaptic signaling/neuron activity.Proteomic analysis demonstrated a dominant effect of IL-4 over IL-13 on inflammatory cell recruitment to the olfactory epithelium and showed activation of neuroinflammation pathways by IL-4, but not IL-13.Finally, IL-4Rα blockade with the dupilumab surrogate restored immune homeostasis and olfactory receptors in olfactory epithelium.Conclusions: IL-4 induces transcriptome and proteome changes suggestive of neuroinflammation and altered olfactory/calcium signaling in mouse olfactory epithelium.These findings provide mechanistic insight into IL-4-evoked loss of smell in mice and importance of IL4Rα signaling in smell restoration.

Background:
The intersection of cancers and IEI related genes has been of interest to immunologists and oncologists for years.However, currently, the details of the role of IEI associated molecular alterations in the genesis and progression of cancer remain unknown.In this study we aim to identify distinct expression signatures of these genes in tumour tissues to further understand this phenomenon.Methods: The TCGAbiolinks R package was used to evaluate the genomic data from 28 different tumors in the Cancer Genome Atlas database.For comparison, healthy tissue samples were incorporated from the Genotype-Tissue Expression Project (GTEx).Using this approach, we performed differential gene expression analysis using the limma-voom and edgeR pipelines through TCGAbiolinks.Each cancer type was examined with its respective healthy tissue.These genes were subjected to pathway enrichment analysis using the pathfinder R package.Examination of somatic mutations within each cancer type was also conducted.Further analysis was restricted to 472 IEI-related genes, which are curated from the Fulgent Genetics Comprehensive PID Panel.Results: Our findings revealed that among the 472 IEI-related genes, 151 (32%) were upregulated and 88 (18.6%) were downregulated across all 28 TCGA datasets compared to GTEx.Cancers that had the greatest number of IEI-related genes differentially expressed were Diffuse Large B-cell Lymphoma, Testicular Germ Cell Tumours, Pancreatic Adenocarcinoma, and Skin Cutaneous Melanoma.Interestingly, genes encoding distinct complement components were predominantly downregulated in most cancers.Mutational analysis further identified a distinct IEI gene signature within individual cancer types.Kaplan-Meier survival plots identified a unique gene set that significantly stratified overall survival rates.Conclusions: Our results showed that the differential expression of certain IRI-related genes may be associated with oncogenic processes and aggressive behavior in malignancies.We discuss the potential mechanisms and implications of these findings to cancer pathophysiology.
Background: Anaphylaxis due to rodent bites is a rare occurrence.Guinea pigs are a species of rodents that have been popular as pets and in research laboratories.There have been no reported cases of anaphylaxis due to guinea pig bites.Case presentation: An 18-year-old male acquired guinea pigs as pets when they were newly born.A few months later, he started noting nasal pruritus and rhinorrhea when he was in contact with the guinea pigs.18 months after acquiring the guinea pigs one of them bit him on the left index finger.He immediately started to have rhinorrhea, nasal congestion and pruritus then he started to develop pharyngeal pruritus and a feeling of tightness in the upper airway.His symptoms progressed to difficulty breathing and he also vomited twice.He had no skin rash and no cardiovascular symptoms.He was taken to his place of work (a restaurant) that was stocked with epinephrine autoinjectors and epinephrine was administered about 30 min after the bite.His symptoms resolved completely within a few minutes.He was taken by ambulance to the ER, his first documented vital signs were 4 h after the incident and were all within normal.He was discharged home after a short period of observation.There were no other possible triggers of his reaction and no noted co-factors for a more severe reaction.When he presented for evaluation, he was well.Skin prick testing showed a 0 mm wheal to normal saline, 3 mm wheal to histamine, and a 7 mm wheal to guinea pig epithelium extract.Specific IgE to guinea pig epithelium was 8.05 kU/L.Conclusions: Our patient's history and investigations are in keeping with a diagnosis of anaphylaxis due to the bite of a guinea pig and provides further evidence of the risk of anaphylaxis when dealing with rodents.
Background: Cannabis use has become increasingly popular since its legalization.In 2022, 19% of Canadians over 16 years reporting use over the past 30 days.Cannabis is associated with an extensive spectrum of cross-reactivity with fruits and vegetables through a phenomenon known as cannabis-fruit/vegetable syndrome.While most patients are co-sensitized with cross-reactive pollen, we present a unique case of cannabis-fruit/vegetable syndrome without birch pollen co-sensitization.
Case presentation: Since 2021, a 26-year-old female with intermittent cannabis smoking began noticing IgE mediated symptoms when eating previously tolerated fruits within the birch pollen family.Her first instance was with fresh cherries where she instantly experienced ocular/throat pruritus and generalized urticaria.In 2022, she had similar reactions to fresh peaches and raspberries.She also began experiencing immediate ocular/throat pruritus with Cannabis sativa but not with Cannabis indica.Her fresh fruit skin test was positive for nectarine (10 mm), plum (6 mm), raspberry (12 mm), blackberry (6 mm), and both Cannabis sativa (7 mm) and indica (11 mm).Her environmental panel was negative to common grass, tree and weed pollens.She was prescribed an epinephrine autoinjector given her systemic symptoms.Conclusions: Multiple potential allergens including non-specific lipid transfer proteins (nsLTP), thaumatin-like protein, ribulose-1,5-bisphosphate carboxylase oxygenase, and oxygen evolving enhancer protein are thought to be contributors to cannabis allergies.Of these, nsLTP is a pan-allergen found ubiquitously throughout the plant kingdom, potentially explaining cross activities between cannabis, fruits, and vegetables.Our case of cannabis-fruit/vegetable syndrome in an otherwise healthy individual is interesting as her skin testing showed no reaction against common pollens, specifically birch, a well-known aeroallergen to cross-react with cherries, peaches, and plums.These findings suggest the patient became primary sensitized through cannabis.With increasing cannabis accessibility, more research is needed to study not only health implications, but also its culprit allergens for more widespread clinical testing and treatment in upcoming years.All participants/their guardians gave written and/or oral informed consent to participate and to be published.Background: Since the first case of transplant acquired food allergy (TAFA) reported in the 1990s, TAFA has been increasingly recognized in solid organs transplantation.Due to the concern of anaphylaxis, acquiring food allergy significantly impact patients' lives.There have been many cases of IgE mediated food allergy transmission post-solid organ transplant most predominantly in pediatric liver transplant recipients.While such transmissions have been reported in lung, heart and pancreatic transplant, TAFA in solitary renal transplants are very rare.
Case presentation: Here we report a case of 61-year-old female with history of end stage renal disease secondary to diabetic nephropathy who underwent recent solitary renal transplant two months prior to presentation to the allergy clinic.She had known childhood history of dust mite sensitization without clinical symptoms but had no IgE mediated hypersensitivity to shellfish prior to transplant.She was started on Tacrolimus, Mycophenolate Mofetil and prednisone after transplant for immunosuppression.It was disclosed to her that the donor had serious shellfish allergy and a question was raised whether or not allergy could be transferred to the recipient.Due to abundance of caution, she avoided shellfish until she could be evaluated in the allergy clinic.Interestingly, percutaneous skin testing revealed immediate hypersensitivity to shellfish believed to be acquired post transplantation.Further testing revealed elevated shellfish specific IgE level in her serum.Oral challenge was not pursued as intradermal skin testing revealed large positive reaction with a wheal diameter of 12 mm to fresh shrimp.Conclusions: Based on the paucity of published cases, incidences of TAFA in solitary renal transplant patients are exceedingly rare.Due to the serious consequences of allergic reaction, this raises the importance of disclosure of allergic history as part of transplant screening, as well as, implementing appropriate protocol and patient education to reduce the risk to the recipient.All participants/their guardians gave written and/or oral informed consent to participate and to be published.Background: Various types of allergic reactions to leech bite have been reported including local reactions, type IV hypersensitivity reactions, and anaphylaxis [1].However, there are no published studies that have characterized the allergenic components of leech bite or examined patterns of cross-reactivity [1].

Case Presentation:
We describe a 10-year-old boy with a past history of eczema and delayed local reactions to leech bite, who developed anaphylaxis to a bite from a freshwater leech in southern Ontario.Skin prick testing to mashed frozen leech (placobdella rugosa and macrobdella decora) collected from the lake was positive and the patient also developed malaise and lightheadedness requiring administration of IM epinephrine × 1.Two years later, he also developed anaphylaxis to a hymenoptera sting, with venom skin testing positive to white faced hornet, paper wasp, yellow hornet, and yellow jacket.Baseline serum tryptase was normal on two occasions (4.1 and 4.0 ng/mL).Specific IgE testing using ALEX chip assay was positive to American house dust mite, European house dust mite, paper wasp, yellow jacket, common mussel, house cricket, migratory locust, and mealworm.Fresh leech from the lake was collected and protein was extracted and identified using Western blots and mass spectrometry.Several proteins were identified, with a number sharing homologies with dust mite, finned fish, and shellfish.Conclusions: This is the first attempt at characterizing leech salivary proteins and characterizing patterns of cross-reactivity.Basophil activation testing is in progress to characterize major leech salivary proteins causing anaphylaxis as well as exploration of possible cross reactivity between leech and hymenoptera venom.All participants/their guardians gave written and/or oral informed consent to participate and to be published.Background: Sweet's syndrome was originally described in 1964 as an acute inflammatory skin eruption with fever and leukocytosis [1].A bullous variant of Sweet's syndrome has also been described, which is more commonly associated with malignancy [2].Multiple medications have been associated with a drug-induced form of Sweet's syndrome [2,3].Case presentation: An 81-year-old woman with crystalline arthritis began allopurinol alongside ongoing methotrexate treatment.

Reference
She had been on long-term hydralazine for hypertension.Two weeks later, she developed a flare of arthritis and hand edema and started a short course prednisone taper.Concurrently, she was admitted to the hospital for diverticulitis.On admission, prednisone was discontinued.The patient subsequently developed violaceous, edematous plaques and bullae on the extremities.She also had conjunctivitis, chemosis, and mucositis.The patient's vitals were within normal limits.Bloodwork showed leukocytosis with neutrophilia (peak 13.3 × 10 9 cells/L) but no eosinophilia.Creatinine peaked at 203 umol/L from baseline, while liver enzymes (ALT 171 U/L, ALP 360 U/L, GGT 166 U/L) were elevated with normal bilirubin.
The CRP reached a maximum of 260 mg/L.Abdominal ultrasound was normal, and blood cultures were negative.HLA-B5801 testing was negative.Skin biopsies showed neutrophilic infiltrates suggestive of Sweet's syndrome.Malignancy screens were up-todate with normal SPEP results.Methotrexate was stopped due to mucositis.The patient was restarted on prednisone at 50 mg daily, gradually tapering.The patient also received intravenous hydration.
Renal and hepatic abnormalities resolved with treatment.Presently, the patient is being monitored for recurrence while on tapering prednisone.
Conclusions: Drug-induced Sweet's syndrome is an unusual hypersensitivity reaction.Previous reports have associated hydralazine [4] and allopurinol [5] with similar reactions.Although uncommon, bullous lesions can be present.Along with other severe adverse cutaneous reactions, clinicians should consider drug-induced Sweet's syndrome in cases of multi-organ blistering drug reactions.All participants/their guardians gave written and/or oral informed consent to participate and to be published.

Inflammation of actinic keratoses induced by subcutaneous immunoglobulin therapy
Arun Dhir 1 , Catherine Biggs 2 , Persia Pourshahnazari Background: Actinic keratoses (AK) are common erythematous papules with scale that occur on sun-damaged skin and may progress to squamous cell carcinoma.Inflammation of actinic keratosis has been reported as a side effect of systemic chemotherapies.Cutaneous reactions (e.g.urticaria, injection site reactions) have been associated with immunoglobulin replacement therapy, including subcutaneous immunoglobulin (SCIG).However, inflammation of actinic keratoses due to immunoglobulin therapy has not been previously reported.
Case presentation: A 76-year-old male with MPO-positive ANCAassociated vasculitis developed hypogammaglobulinemia secondary to rituximab.Medical history included chronic obstructive pulmonary disease and actinic keratoses with prior SCC resection.Recurrent respiratory infections and low IgG levels prompted SCIG therapy at 0.1 g/kg/week.At this time, the patient was tapering off of prednisone.
No other medications were started.Eight weeks into SCIG therapy, and near the end of the prednisone taper, the patient developed a diffuse eruption of erythematous, pruritic papules and plaques.Bloodwork showed no eosinophilia or liver/kidney dysfunction, though CRP was elevated at 9.8 mg/L.Given the history of vasculitis, prednisone was initiated empirically at 20 mg/day with a 5 mg/week taper.Topical betamethasone 0.1% ointment and oral bilastine were also given.As immunoglobulin levels were robust, SCIG therapy was temporarily halted.Dermatology performed a skin biopsy, suggesting actinic keratoses without signs of a drug reaction.The lesions were thus thought to be inflamed actinic keratoses.The patient's condition improved within a week.Gradual resumption of SCIG therapy with close monitoring is planned given potential recurrence.Conclusions: Inflammation of actinic keratoses induced by SCIG is a novel phenomenon.Our patient was successfully treated with oral and topical steroids, with a plan to gradually restart SCIG therapy.This may represent a rare reaction due to immune system reconstitution, though the specific mechanism is unclear.
All participants/their guardians gave written and/or oral informed consent to participate and to be published.Case presentation: A 33-year-old woman with a medical history of allergic rhinitis and experienced intermittent oral pruritus when consuming raw fruits, vegetables, peanuts, and tree nuts, with occasional lip swelling.Cooking food alleviated her symptoms.

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Previously, the patient had an immediate oral pruritus reaction to raw tomatillos in salsa.Thirty minutes later, she developed progressive abdominal pain.She took ibuprofen with no relief.Approximately 4 h later, as her abdominal pain was ongoing, she presented to an emergency department.Subsequently, she developed systemic urticaria and dyspnea, promptly treated with epinephrine with instant relief.Following this event, the patient avoided tomatillos but consumed tomatoes and used NSAIDs without experiencing any adverse reactions.She had another reaction to a meal containing raw tomatillos, developing oral pruritus and abdominal pain one hour later, improving with diphenhydramine.
Skin testing was positive to birch and hazelnut extracts (4 mm) but negative to tomato extract, peanuts, and other tree nuts.Fresh food skin testing was positive to tomatillo (12 mm) but negative to tomato.Subsequently, the patient received a diagnosis of tomatillo allergy concurrent with a pollen-food allergy syndrome involving other birch cross-reactive foods.The patient was advised to strictly avoid tomatillos and to carry an epinephrine autoinjector.In the absence of systemic symptoms, continued cautious consumption of birch cross-reactive foods was permitted.
Conclusions: Tomatillos are a rare food allergen.As commercial extracts are not available, fresh food testing is required to confirm the diagnosis.Cross-reactivity with tomatoes may not be present.Further studies are necessary to identify the underlying allergenic protein components.All participants/their guardians gave written and/or oral informed consent to participate and to be published.

An unexpected culprit of delayed drug hypersensitivity reaction
Erika Y. Lee 1,2 , Jackie Campbell 1 , Jonathan Zipursky Case presentation: A 37-year-old woman was referred for a suspected labetalol allergy.She was started on oral labetalol in the third trimester for gestational hypertension.After approximately 6 weeks on the drug, she noticed a rash in her groin.On the following day, she underwent an urgent caesarian delivery and received Penicillin G and oxytocin.
In the ensuing days, she developed a generalized morbilliform rash, fever and facial swelling, and was subsequently readmitted to the hospital.Laboratory investigations showed no evidence of peripheral eosinophilia nor internal organ involvement.Labetalol, which was suspected to be the culprit due to the continuous exposure and timing of the reaction, was discontinued, and the rash improved in a week.
In clinic, we performed IDT to labetalol (0.05 mg/mL and 0.5 mg/ mL), penicillin G (10,000 U/mL), ampicillin (20 mg/mL), and Pre-Pen.The patient had negative IDT to labetalol at immediate and delayed readings.The IDT to penicillins was negative at 20 min but became positive to ampicillin and penicillin G at 24 h.She later tolerated an oral challenge to labetalol.She was therefore diagnosed with penicillin allergy and counselled to avoid penicillins.Conclusions: Despite a clinical history suggestive of a delayed DHR to labetalol, our skin testing identified penicillin as the actual culprit.The case illustrates the role of drug allergy testing to assist with DHR diagnosis and highlights the importance of referring patients to a drug allergy clinic to identify potential culprits and verify relevant drug allergies.
All participants/their guardians gave written and/or oral informed consent to participate and to be published.Background: Current management of food protein-induced enterocolitis syndrome (FPIES) can be burdensome as it involves strict avoidance and a resource-intensive oral food challenge (OFC) when older.While the use of ladders has been successful in treating milder IgE-mediated cow's milk and egg allergies, there is limited evidence for its use in the management of FPIES to foods such as peanut.We present two infants with FPIES to both egg and peanut, who after being managed with the Canadian Egg Ladder were successfully started on a similar ladder approach to peanut.Case presentation: Case 1: 6-month-old male with several episodes of severe vomiting, diarrhea, and lethargy 2 h after ingestion of egg.At 8-months, multiple episodes of projectile vomiting 2-3 h after ingestion of peanut.Skin prick test (SPT) was mildly positive to egg and negative to peanuts.Patient successfully completed the egg ladder by 2-years but repeat trials of peanut every few months still caused delayed vomiting.Recently was successfully started on a peanut ladder.Case 2: 6-month-old male with 3 episodes of severe vomiting 2 h after ingestion of egg, and 2 episodes of profuse vomiting 2-3 h after ingestion of peanut.SPT negative to egg and peanut.Successfully completed both the egg ladder and peanut ladder by 1-year follow-up.
Conclusions: These two cases of egg and peanut FPIES managed with a ladder approach reduce/eliminate the need for burdensome exit OFCs, and are a safe and effective alternative to strict avoidance.Additionally, this approach could potentially prevent the development of IgE-mediated allergy by allowing earlier and continued introduction of allergens.Larger studies assessing the use of a ladder approach for the management of FPIES to foods other than cow's milk and egg should be considered.All participants/their guardians gave written and/or oral informed consent to participate and to be published.Case presentation: Here, we present a 61-year old male who reported 2 episodes of severe facial angioedema within 48-72 h after Venom immunotherapy (VIT).On both occasions, he described asymmetrical tongue swelling following VIT which was not relieved by 80 mg of bilastine and lasting for approximately 1-2 days.Interestingly, he had not had an adverse reaction during the first 11 months of VIT and denied any symptoms of infection, trauma or use of suspicious medications such as ACE-inhibitors.Laboratory tests demonstrated decreased C1-INH function and C4 level, during both events.While the later age of onset was initially suggestive of acquired angioedema, this patient had no signs or symptoms of lymphoma or autoimmune disease and had an unremarkable serum protein electrophoresis (SPEP).Moreover, his sister had an episode of angioedema in her childhood requiring a tracheostomy, suggesting a genetic component and shifting the provisional diagnosis to HAE Type II.

Conclusions:
We are currently awaiting further labs to rule out acquired angioedema.The patient's family members have also been asked to undergo testing for HAE.Regardless of the ultimate diagnosis, this report outlines an unusual case of bradykinin-induced angioedema triggered by VIT.The patient continues to be followed monthly for VIT at a reduced dose while we secure Icatibant for management of acute attacks.All participants/their guardians gave written and/or oral informed consent to participate and to be published.Background: Allergic reactions to deer meat is known in the context of the alpha-gal syndrome.Patients typically react to other mammalian meats such as beef, lamb and pork.Reactions are delayed, occurring a few hours after ingestion.Ticks, such as lone star tick, has been identified as a cause of sensitization to the alpha-gal antigen.

A case report of deer meat anaphylaxis in a child
In contrast, no case of IgE-mediated allergy to deer meat has been reported to our knowledge.

Case presentation:
We describe a case of an 18-month-old girl with anaphylaxis following ingestion of deer meat.She is an atopic child with personal history of mild atopic dermatitis and multiple food allergies (milk, peanut and shellfish).She is on peanut oral immunotherapy and on the Canadian milk ladder, which she tolerates both well.After the first exposure to deer meat around 10 months of age, she developed urticaria and emesis within minutes of ingestion.Parents were suspicious for cross contamination with shellfish as the pan used to cook the deer meat was previously used to cook shellfish.Accordingly, deer meat was not avoided.On second ingestion, she developed a very similar reaction.Parents were then suspicious that butter might have been used during the preparation.Finally, on third exposure, great caution was used during the preparation of the meat to avoid any cross contamination with her known allergens.Despite this, she developed the same symptoms with immediate hives and vomiting.She tolerates other mammalian meats such as beef, pork and lamb.She has never been bit by a tick.Skin testing was positive to cooked deer meat (5 mm), with a positive histamine and negative saline control.She continues to avoid deer meat and carry an epinephrine auto-injector at all times.Conclusions: Anaphylaxis to mammalian meats outside the context of alpha-gal syndrome is very rare but recognition is important.All participants/their guardians gave written and/or oral informed consent to participate and to be published.Background: Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease.It is characterized by circulating autoantibodies toward the basement membrane antigens BP180 and BP230 [1].Patients present with tense blisters on a background of underlying erythematous base.Different triggers have been identified for BP including medications, infections, malignancies, and vaccinations [2].Post-vaccination BP is rare with a few case reports of new onset BP triggered by diphtheria, tetanus, influenza, pneumococcal, whooping cough, poliomyelitis, meningococcal, hepatitis B, BCG, and rabies vaccinations [3].In patients with underlying autoimmune blistering skin disease there was evidence of a disease flare after receiving Pfizer-BioNTech vaccine during a remission period [4].

Case presentation:
We describe the first case in Canada of a 54-yearold male who has no known medical problems and is not on any prescribed medications who presented four weeks following his 5th COVID booster with widespread erythematous rash.His family history was negative for significant diseases and skin disorders.He was initially treated with systemic corticosteroid (Prednisone 50 mg) however the rash spread to his perineum and inguinal folds, and he started to develop tense blisters.His Eosinophil count peaked at 2.33.A skin biopsy confirmed the diagnosis of BP, with direct positive serum immunofluorescence showing a linear band of C3 along the basement membrane.His prednisone dose was increased to

Case presentation:
We present a 7-month-old female seen 10 days post-liver transplantation for biliary atresia.Her donor's cause of death was anaphylaxis due to a suspected pine-nut exposure.Donor allergies listed included many priority allergens such as cow's milk, soy, sesame, peanuts, treenuts, "gluten" (wheat) including legumes and fruits.No further information was accessible due to donor's anonymity.
Post-operatively, her diet consisted of elemental formula exclusively and therefore, the Allergy team was consulted to advise on food introduction given her risk factors for developing transplant acquired food allergies.She was receiving Tacrolimus, methylprednisolone and Benadryl which limited skin testing at the time.Allergen-specific IgE was drawn to each listed food allergen including pine-nuts which were negative (< 0.35 kU/l).We recommended introducing a single food allergen at each meal separated by a few hours to facilitate timely introduction of listed foods.For pine-nuts specifically, we suggested an oral graded challenge only after negative skin testing which would be facilitated as an outpatient with strict avoidance in the interim.Her parents were counselled to always carry an epinephrine autoinjector.Conclusions: Management of transplant acquired food allergies can be challenging especially in the context of a donor deceased from fatal anaphylaxis, a restrictive list of suspected food allergies and limited information due to donor anonymity.Our approach would facilitate introduction of many listed food allergies without delays that could compromise growth and development of pediatric patients post-transplant.All participants/their guardians gave written and/or oral informed consent to participate and to be published.Background: Serum sickness-like reactions (SSLRs) are non-immune complex-mediated presentations characterized by rash, fever, and polyarthralgias [1].SSLRs are triggered by viral infections, vaccines, and drugs such as amoxicillin [1,2].SSLRs differ from serum sickness (SS) in that they do not involve immune complexes and are not IgEmediated [3].SS and SSLRs share clinical features, hence distinguishing them can be difficult.He was treated with 5 mg oral cetirizine daily and 1 mg/kg oral prednisone which improved his rash and angioedema.The allergy and immunology consult service suggested up to 4 times the usual dose of second-generation antihistamines PRN for pruritus.At the Adverse Drug Reactions clinic, skin testing to penicillin and ampicillin was negative; his parents decided to defer an oral challenge.
A diagnosis of probable SSLR to amoxicillin was made.Conclusions: Our case report demonstrates that patients with previous tolerance to Amoxicillin can develop SSLR with repeat exposure, thereby expanding our understanding of the range of adverse reactions which can be seen even with previously tolerated drugs.Healthcare providers need to remain vigilant to drug reactions and correctly diagnose SSLR, since safe reuse of Amoxicillin is possible even in this situation.All participants/their guardians gave written and/or oral informed consent to participate and to be published.
Background: Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction (SCAR) that occurs within 2-8 weeks following drug exposure.The management may prove challenging, particularly in patients with comorbidities requiring multiple medications.The optimal approach aims to identify the culprit drug with minimal restriction of potentially useful medications.In this study, we discuss the in vivo and ex vivo workup for a patient with DRESS syndrome associated with broad-spectrum antibiotics.

Case presentation:
The patient is a 76-year-old male diagnosed with DRESS syndrome (RegiSCAR Case presentation: We present a case report of a 43-year-old woman who experienced two episodes of anaphylaxis without an apparent trigger.On both occasions, the episodes occurred shortly after consuming breakfast, a protein shake and a sports recovery drink.The initial presentation occurred within thirty minutes, characterized by dyspnea, pre-syncope, and generalized pruritus, resolving with the administration of steroids and antihistamines.The second episode developed within minutes, presenting with neck angioedema, dyspnea, and pre-syncope, requiring two epinephrine injections.It was subsequently revealed that the protein shake contained rice protein, while the sports recovery drink contained brown rice syrup.There were no cofactors such as exercise or NSAIDS.We considered the possibility of a mast cell disorder, but her baseline tryptase was normal.
Skin prick testing yielded positive results to rice milk.To confirm the diagnosis, an oral challenge with rice milk was performed.Within ten minutes of ingesting 0.2 mL of rice milk, the patient developed hives and angioedema.Serum-specific IgE testing revealed positive results for wheat, buckwheat, and barley.The patient has since avoided rice and all other grains without experiencing anaphylaxis.Conclusions: This case report serves as an illustration of anaphylaxis without an identifiable trigger, emphasizing the importance of considering uncommon allergens and concealed sources during the diagnostic evaluation process.All participants/their guardians gave written and/or oral informed consent to participate and to be published.
Background: Asthma and atopy are rapidly becoming significant causes of mortality and morbidity in Africa.However, they are largely undiagnosed and undertreated due to both poor access to allergist care and remarkably few allergists on the African continent [1].Data on anaphylaxis is extremely limited with no register-based African studies [2].One small cohort study showed that most anaphylaxis episodes were managed solely by a layperson and epinephrine was rarely administered even by healthcare professionals [3] Background: Patient-reported penicillin allergies are common but often inaccurate, leading to suboptimal antibiotic selection, worse patient outcomes, and increased healthcare expenses.Limited availability of Allergy-Immunology subspecialists and uncertainty among non-allergist physicians contribute to difficulty in assessing these allergies.Methods: We aimed to develop an accessible virtual clinical decision tool for accurately assessing the risk of true penicillin allergy and appropriateness for a challenge based on the previously validated PEN-FAST decision rule.Additionally, we used OpenAI's large language model to create a preliminary assessment chatbot for patients.

Results:
We created a user-friendly website [https:// penic illin aller gy.ca/] with a risk stratification tool for patients and healthcare providers that automatically generates a personalized referral note, including a preliminary assessment that is generated for their personal doctor.It also offers a physician-led protocol for direct oral challenges in low-risk patients and high-quality resources for patients and physicians.We also developed a high-fidelity proof-of-concept chatbot using Chat-GPT-3.5 to guide patients through the decision tool.Conclusions: Penicillin allergy labels are prevalent but often inaccurate.Enhancing accessibility to user-friendly tools for providers and patients to evaluate these labels and determine the need for further testing could substantially impact antibiotic stewardship, patient outcomes, and healthcare costs.This tool will be used in a future QI initiative to test the feasibility of primary care de-labelling.Background: Data on food protein induced enterocolitis syndrome (FPIES) are sparse.We aimed to evaluate sociodemographic characteristics, co-morbidities, and triggers of children presenting with FPIES, as well as their tolerance to baked goods.Methods: Children with physician-diagnosed FPIES were enrolled and followed at the Montreal Children's Hospital and an affiliated clinic.Families were queried on the food trigger and co-morbidities, as well as clinical characteristics of reaction and management.A severe reaction was defined as vomiting 4 or more times, altered behaviour/ lethargy, pallor, dehydration, and need for IV fluids [1].

Conclusions
Results: Of the 339 patients recruited, 48.1% were male.The median age of symptom onset was 10.0 years old (IQR 10.00).Among all, 17.4% had spontaneous CU, 82.6% had inducible forms and none had coexisting spontaneous and inducible forms.Approximately 15.0% of patients had asthma, while the same percentage had atopic dermatitis.Treatment involved antihistamines for 78.2% of patients and omalizumab for 4.1%.A single patient exhibited an elevated tryptase level of 13.7 mcg/l, surpassing the average cohort tryptase level of 3.9 mcg/l.HaT diagnosis was established through genetic testing, which revealed an additional copy of alpha tryptase encoded by the TPSAB1 gene.Genetic assessment for first degree family members revealed three more cases with HaT: the father (intermittent hives), the brother (intermittent itchiness and hives), and the sister (recurrent syncope and ketotic hypoglycemia).The patient's hives were well controlled with omalizumab.
Background: Hereditary angioedema (HAE) is a rare genetic disease that leads to painful swelling of the upper airway, gastrointestinal tract, and extremities.Long-term prophylaxis (LTP) to prevent angioedema episodes is the cornerstone of modern disease management.Berolostat, an oral plasma kallikrein inhibitor, was approved for LTP by Health Canada in 2022.

Methods:
We conducted a retrospective study examining the effectiveness and adverse effects of berotralstat in a real-world setting.
Data on attack frequency, disease control, and adverse events before and after starting berotralstat were collected.Disease control was measured using the Angioedema Control Test (AECT), a validated patient-reported instrument with scores between 0 to 16, with higher values indicating better control [1].Patient satisfaction with treatment was scored on a 5-point Likert scale with 1 representing very unsatisfied and 5 representing very satisfied with therapy.
Results: Between June, 2022 and May, 2023, 8 patients with HAE type 1 or type 2 were prescribed berotralstat 150 mg once daily.Effectiveness data were available for 7 patients who continued the drug for at least 3 months, 4 of whom switched to berotralstat from plasma-derived C1 inhibitor LTP.In these 7 patients, the average number of attacks per month decreased from 3.3 to 1.6 (p < 0.05), representing a ~ 52% reduction in attack frequency, similar to the 57% reduction observed in a phase 3 registration trial [2].Median AECT score numerically improved from 8 to 13 (p = 0.0781).Of the 8 patients who started berotralstat, 3 reported no adverse effects and 5 experienced gastrointestinal adverse effects, which were mild or transient in 3 and led to discontinuation in 1.Average treatment satisfaction was between satisfied and very satisfied at 4. Background: Hereditary angioedema with a specific mutation in the plasminogen gene (HAE-PLG) is a recently identified subtype of hereditary angioedema (HAE) characterized by bradykinin-mediated angioedema [1].It is inherited in an autosomal dominant manner, and women are more commonly affected than men.Methods: We conducted a retrospective chart review of four patients with HAE-PLG, confirmed by genetic testing, who were undergoing treatment in British Columbia, Canada.Results: All four patients were female, with three patients belonging to the same family.The average age of symptom onset was 27.5 years (range: 19-51 years), and the average age at diagnosis was 42.75 years (range: 26-56 years).All patients experienced oropharyngeal attacks.One patient required two ICU admissions and one intubation.Three patients (75%) reported symptoms related to exogenous estrogen.One patient experienced more frequent symptoms during pregnancy.Two patients (50%) reported more frequent attacks after menopause.
One patient has responded well to on-demand antihistamines alone, suggesting concurrent idiopathic histamine-mediated angioedema.
Another patient received a combination of corticosteroids and antihistamines with potential benefit.Two patients received plasmaderived C1-esterase with good response.These two patients have also responded well to icatibant.One patient had a partial response to tranexamic acid.One patient has been initiated on berotralstat, with ongoing evaluation of its effectiveness.Conclusions: While it was previously believed that estrogens played a less significant role in HAE-PLG compared to patients with specific mutations in the F12 gene (HAE-FXII) [1,2], our patients reported a high rate of estrogen-associated symptoms.Two patients also reported extensive menopause-related angioedema, which has not been described previously.A variety of treatment options have been used in our cohort, with icatibant and plasma-derived C1-INH appearing to be particularly effective.Future research is needed to further comprehend and improve the management of HAE-PLG.

32
Optimization of a novel casein-specific anaphylactic mouse model Wei Zhao, Eisha Ahmed, Nicholas Vonniessen, Casey Cohen, Bruce Mazer The Research Institute of the McGill University Health Centre and the Department of Pediatrics, Faculty of Medicine, McGill University, Montreal, QC Correspondence: Wei Zhao Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):32

Reference 1 .
Boyce JA, Assa'ad A, Burks AW, et al.Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAIDsponsored expert panel.J Allergy Clin Immunol.2010;126(6 Suppl):S1-58.

54 A rare case of transfer of Shellfish allergy from allergic donor to anergic recipient
in Solitary Renal Transplant Jung Min (Julie) Hong, Lundy McKibbin University of Manitoba Department of Internal Medicine, Winnipeg, MB Correspondence: Jung Min (Julie) Hong Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):54

3 1
Drug Safety Clinic, Sunnybrook Health Sciences Centre, Toronto, ON; 2 Division of Clinical Immunology & Allergy, Department of Medicine, University of Toronto, Toronto, ON; 3 Division of Clinical Pharmacology & Toxicology, Sunnybrook Health Sciences Centre, Toronto, ON Correspondence: Erika Y. Lee Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):64 Background: Delayed drug hypersensitivity reactions (DHR) are T-cell mediated with prominent skin findings that usually manifest days to weeks after drug exposure.Drug allergy testing can assist with the diagnosis and confirmation of the culprit drug.Common testing for delayed DHR includes patch testing and intradermal testing (IDT), sometimes followed by drug provocation testing (DPT).

65
Utilizing a ladder approach for the management of peanut food protein-induced enterocolitis syndrome (FPIES) Nicole A. Mar, Edmond S. Chan, Stephanie C. Erdle Division of Allergy, Department of Pediatrics, University of British Columbia, BC Children's Hospital, Vancouver, BC Correspondence: Nicole A. Mar Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):65 Junghoon Ko, Juan C. Ruiz University of British Columbia, Vancouver, BC Correspondence: Junghoon Ko Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):66 Background: Bradykinin-induced angioedema is often classified into three types: hereditary (HAE), acquired, and drug-induced.HAE involves decreased production or function (Type I vs II) of the C1 esterase inhibitor (C1-INH) protein responsible for breaking down bradykinin whereas the acquired form is associated with overconsumption of C1-INH.Clinically, while both HAE and acquired angioedema are characterized by cutaneous, respiratory and/or gastrointestinal manifestations, HAE tends to present earlier, usually in adolescence, and acquired angioedema is often associated with other lymphoproliferative or autoimmune disorders.Common triggers for both include stress, trauma, and infection.

3 .
Conclusions: Berotralstat is an effective agent for long-term prophylaxis in HAE.Most patients experienced no adverse effects or mild, transient gastrointestinal symptoms.96 Retrospective chart review of four patients with hereditary angioedema with specific plasminogen gene mutation Arun Dhir, Shamim Wadiwalla, Amin Kanani Division of Allergy and Immunology, Department of Medicine, University of British Columbia, Vancouver, BC Correspondence: Arun Dhir Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):96

Correspondence: Amy Plessis Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):16
Department of Pediatrics, Faculty of Medicine, University of British Columbia Island Medical Program, Victoria, BC

Asthma & Clinical Immunology 2024, 20(Suppl 1):34 Background
Epinephrine administrations occurred during build-up (75.4%; n = 95) and maintenance (24.6%; n = 31).There were 21 patients (23.9%) who received epinephrine on multiple occasions (2 occasions, 10.2%; 3 occasions, 9.1%; 4 occasions, 2.3%; 5 occasions, 2.3%).Of the 88 patients who received epinephrine, 42 (47.7%)had ≥ 1 cofactors present at the time of their reaction.The most common were: comorbid illness (40.5%), vigorous exercise (23.8%), and dosing on an empty stomach (23.8%).Other cofactors included: Dosing errors (n = 7), Emotional stress/anxiety (n = 3), and dosing during pollen season in patients who are grass-pollen allergic (n = 2).Conclusions: Comorbid illness, vigorous exercise, and taking OIT doses on an empty stomach appear to be important cofactors present at the time of allergic reaction with epinephrine administration.A discussion about cofactors should be included in the educational aspect of the enrollment process for OIT.Future research will examine potential differences on the impact of cofactors on reactions during build-up versus maintenance, and whether there are other risk factors for epinephrine use beyond cofactors.
1 , Edmond S. Chan 1 , Raymond Mak 1 , Tiffany Wong 1 , Stephanie Erdle 1 , Scott B. Cameron 1 , Joanne Yeung 1 , Sandeep Kapur 2 , Mary McHenry 2 , Gregory A. Rex 2 , Sara Leo 1 , Thomas V. Gerstner 3 , Victoria E. Cook 1 , Lianne Soller 1 1 University of British Columbia, Vancouver, BC; 2 Dalhousie University, Halifax, NS; 3 University of Manitoba, Winnipeg, MB Correspondence: Alexandra Baaske Allergy, :Patients may experience reactions requiring epinephrine during oral immunotherapy (OIT) for food allergy, and certain cofactors may reduce the patient's threshold at which they experience symptoms.We examined cofactors reported at the time of epinephrine administration for patients receiving OIT as part of a Canada-wide quality improvement project.Methods: Canadian academic and community allergists administered OIT to predominantly preschool-aged patients.Data collection forms capturing information about epinephrine administration, including whether the patient was on OIT buildup or maintenance, and cofactors present, were analyzed.Results: Between July 1, 2017 and May 16, 2023, 126 epinephrine administration forms were completed for 88 OIT patients.Of these, median age at start of OIT was 47 months (IQR: 30.5, 69.5), 70.5% of patients were male, 78.4% had one or more atopic conditions (asthma, eczema, allergic rhinitis), and 62.5% were receiving single-food OIT.

35 Can patients who required epinephrine after administration of the COVID-19 vaccine safely receive the vaccine in the future
? Sarah K. Lohrenz, Godfrey Lam, Amin Kanani University of British Columbia, Vancouver, BC Correspondence: Sarah K. Lohrenz Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):35Background: Currently the Centers for Disease Control (CDC) and the World Allergy Organization (WAO) recommend against readministration of a second dose of a SARS-CoV-2 mRNA vaccine in those with moderate-severe immediate type reactions.However, accumulating data supports readministration in a supervised setting[1].Methods: We performed a retrospective analysis of patients who were able to tolerate a SARS-CoV-2 mRNA vaccine challenge after receiving epinephrine with their initial dose.Charts were reviewed in allergy/immunology offices in Vancouver from December 14 2020 to November 30, 2022.Results: 9 patients were identified, 8/9 were female, age range was 18-71 years, and the median age was 47 years.All reactions occurred within 1 h of vaccine administration.The most common symptoms reported were dyspnea, cough, dysphagia, oropharyngeal swelling, dizziness, flushing/pruritus, nausea and vomiting.Hypotension was not a prominent feature.7/9 reactions were to the Pfizer vaccine, 1/9 to the Moderna and 1/9 due to AstraZeneca.All patients required between 1-5 doses of epinephrine.7/9 had negative intradermal testing to the SARS-CoV-2 mRNA vaccine, 1 patient had an equivocal test and 1 patient did not undergo testing.All patients (

dose food reintroduction and gradual advancement may be a safe approach in management of mild-to-moderate food protein-induced enterocolitis syndrome to solid foods
Linlei Ye 1 , Samira Jeimy 2 , Timothy K. Vander Leek 3 , Elana Lavine 4 , Tiffany Wong 5 , Stephanie C. Erdle 5 , Victoria E. Cook 5 Current long-term management of acute food proteininduced enterocolitis syndrome (FPIES) involves strict avoidance of the food trigger for 12-18 months, followed by resource-intensive oral food challenges (OFC).However, prolonged avoidance may increase the risk of IgE-mediated food allergy and adversely impacts quality of life.For IgE-mediated food allergy, food ladders have shown success in accelerating tolerance for egg and milk.Our case series evaluated the safety of low-dose food reintroduction and gradual advancement in patients with mild-to-moderate FPIES to solid foods (non-egg, non-milk).
Methods: Between 2020 to 2022, pediatric patients with mild-tomoderate FPIES to solid foods were reintroduced to the food trigger within 6 months after their last reaction.Beginning with a grain-sized amount, portions were gradually increased and provided on a regular basis.Patients were reassessed every 3-6 months, at which time treating allergists collected information on symptoms experienced and provided instructions for dose advancement.If symptoms were experienced, patients returned to the previously tolerated dose.All patients were offered a prescription for ondansetron.Descriptive statistics were analyzed using Excel.Results: Fifteen patients with mild-to-moderate FPIES to solid foods were reintroduced to the offending food at a median time of 3 months (IQR, 2-4) after their last reaction.The most common food trigger was oat (27%, n = 4).All patients successfully tolerated an ageappropriate serving of food within a median duration of 5 months (IQR,[3][4][5][6][7][8].Four (27%) patients experienced symptoms during the intervention, including belching (20%), abdominal discomfort (6.7%), and a single episode of vomiting (6.7%).No patients required acute medical assessment or intravenous fluids.No patient discontinued the intervention.Conclusions: This small case series demonstrated that allergist-guided gradual food reintroduction and advancement within 6 months of the most recent FPIES reaction may be a safe approach in some patients with mild-to-moderate FPIES to solid foods.

37 Safety of home initiation of the Canadian Egg Ladder in children with isolated cutaneous symptoms following egg exposure
Initiation of the ladder by non-allergist providers in patients with isolated cutaneous symptoms after egg exposure may facilitate reintroduction of egg into the diet and reduce the need for allergist assessment.This case series describes safety of home egg ladder initiation in patients with isolated cutaneous symptoms following egg exposure.This case series demonstrates that the egg ladder can safely guide reintroduction in pediatric patients with isolated cutaneous symptoms following egg exposure and provides additional support for the safety of at home ladder initiation.Use of this intervention in low-risk children by non-allergist providers could facilitate earlier reintroduction of egg into the diet and may reduce the need for allergist assessment.
Background: Patients with cutaneous symptoms following egg exposure are often referred to allergy and instructed to avoid egg in all forms.The Canadian Egg Ladder has demonstrated safety in patients with IgE-mediated allergy to egg[1], and home ladder initiation appears to be safe in egg-allergic patients[2].handled by the nurses of the service during clinic hours (n = 843) for 396 children (89.8%) and buy CCAR during evenings and weekends (n = 64) for 45 children (10.2%).The most frequent reasons for calls

CSACI Summer Studentship Award winner Immunology 39 Once-daily oral berotralstat led to improvements in work productivity and activity impairment in patients with hereditary angioedema: results from the APeX-2 randomized phase III trial
Rémi Gagnon 1 , William R. Lumry 2 , Teresa Caballero 3 , Douglas T. Johnston4, Dianne Tomita 4 , Bhavisha Desai 4 , Daniel F. Soteres5  1Clinique spécialisée en allergie de la capitale, Québec, QC;2Allergy and Asthma Specialists of Dallas, Dallas, TX, USA; 3 Hospital Universitario La Paz, Madrid, Spain;4BioCryst Pharmaceuticals, Inc., Durham, NC, USA;Diagnosing CTLA-4 insufficiency facilitates use of life-saving targeted therapies; however, can be hampered by inconclusive genetic testing results.Here we report the clinical presentations and functional validation of novel CTLA4 variants identified at our center.Methods: Patients with clinical phenotypes compatible with CTLA-4 insufficiency and a variant of uncertain significance in CTLA4 were enrolled in the study.Variant significance was analyzed by computational analytical tools and by assessing CTLA-4-mediated transendocytosis of its ligand CD80, using plasmids expressing the variants.Clinical and immunological features were assessed before and after treatment.Results: We studied 2 unrelated families with immune dysregulation and heterozygous variants in CTLA4.Sequencing of a 14-year-old male with a history of infections, Crohn disease, granulomatous and lymphocytic interstitial lung disease, lymphocytic infiltration of the brain, hypogammaglobulinemia, and autoimmune cytopenias revealed a de novo variant in CTLA4 (c.424G>C, p.G142R).Targeted therapy with abatacept in combination with corticosteroids and sirolimus led to dramatic clinical improvement.Functional validation of p.G142R demonstrated impaired CTLA-4-mediated transendocytosis, confirming its pathogenicity.A 2-month-old male infant inherited a novel CTLA4 variant (CTLA4 c.416A>C, p.Y139S) from his father who had undergone genetic testing for a history of autoimmunity and immune deficiency.At the time of genetic diagnosis, the infant had developed autoimmune neutropenia.Both variants are absent from healthy reference populations and are predicted damaging by in silico tools.Conclusions: This report identifies and characterizes 2 novel diseasecausing variants in CTLA4, expanding the genotypic profile of CTLA-4 insufficiency.Our experience highlights the importance of considering inborn errors of immunity when evaluating patients with immune dysregulation, and the value of resolving variants of uncertain significance to confirm diagnoses and advance care.All participants/their guardians gave written and/or oral informed consent to participate and to be published.
5 Asthma & Allergy Associates and Research Center, P.C., Colorado Springs, CO, USA Correspondence: Rémi Gagnon Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):39Background: Berotralstat is a first-line, once-daily (QD) oral prophylaxis for hereditary angioedema (HAE), which has demonstrated sustained attack rate reduction in clinical trials[1].Here we present the impact of berotralstat on work productivity and activity impairment, as measured by the Work Productivity and Activity Impairment (WPAI) Questionnaire, in patients from APeX-2 (NCT03485911).Methods: APeX-2 was a randomized, placebo-controlled, parallel group, Phase III trial that evaluated the efficacy and safety of oral berotralstat 110 and 150 mg in patients ≥ 12 years with type I or II HAE[1, 2].The WPAI Questionnaire was administered at baseline and several predefined visits during the study.The questionnaire consists of absenteeism, presenteeism, work productivity loss, and activity impairment domains.WPAI outcomes are expressed as percentages; higher scores indicate greater impairment or less productivity.A reduction in score indicates improvement.WPAI scores for patients who received berotralstat 150 mg QD from Day 1 are summarized descriptively using mean percentages ± standard error of the mean values.Results: In total, 40 patients received berotralstat 150 mg QD from Day 1. Work productivity loss improved from 36.0 ± 6.16 at baseline (n = 25) to 18.1 ± 5.01 (n = 25), 21.0 ± 5.45 (n = 27), 17.5 ± 5.25 (n = 22), and 1.7 ± 1.67 (n = 12) after 4, 24, 48, and 96 weeks of berotralstat treatment, respectively.Activity impairment improved from 35.8 ± 4.46 at baseline (n = 40) to 17.4 ± 3.78 (n = 38), 21.6 ± 4.23 (n = 38),15.3±4.12 (n = 34), 6.3 ± 3.52 (n = 19) after Methods: In this study, the Hsp27-Nef construct was considered as apromising candidate for HIV-1 vaccine development.To optimize the transfection efficiency of DCs derived from mouse bone marrow cells, a comprehensive approach involving cell heating at three different stages (before, during, and after transfection) was implemented.The cells underwent a 2-h heat treatment at 42 °C.The method that demonstrated the highest efficiency of gene transfer was selected for immunization.Additionally, a subset of DCs was pulsed with Hsp27-Nef protein and subsequently utilized for immunization.Moreover, the heterologous DC DNA prime/DC protein boost regimen was employed for immunization in BALB/c mice.Finally, immune responses were assessed by monitoring antibodies, IFN-γ and IL-5 cytokines, as well as Granzyme B secretion.Results: Our results demonstrated that heat treatment of the cells before transfection for 2 h at 42 °C significantly increased the efficiency of gene transfer in DCs.Moreover, immunization with the heterologous DC DNA prime/DC protein approach utilizing Hsp27-Nef resulted in elevated levels of IgG2a and IFN-γ, which are indicative of Th1 responses, as well as increased secretion of Granzyme B, compared to other immunization strategies.Furthermore, the incorporation of Hsp27 provided an effective means of stimulating robust immune responses.Conclusions:These findings highlight the importance of optimizing transfection conditions for efficient antigen delivery in HIV-1 DC-based vaccine design.Furthermore, the insights gained from this study make a valuable contribution to the ongoing endeavors aimed at developing an effective HIV-1 vaccine.

42 Additional booster doses of COVID-19 vaccine enhance neutralization efficiency against XBB.1.5
Elsa Sakr 1 , Nisha D. Almeida4,6, Ian Schiller5,6, Danbing Ke 1 , Maria Plesa 1 , Marc-André Langlois 3 , Kaberi Dasgupta4,5, Bruce D. Mazer 1,2 1 Translational Research in Respiratory Diseases, Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montréal, QC; 2 Department of Pediatrics, Faculty of Medicine and Health Sciences, McGill University, Montréal, QC; 3 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON; 4 Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montréal, QC; 5 Center for Outcomes Research and Evaluation, Research Institute of the McGill University Health Center, Receiving additional boosters of the COVID-19 vaccine elicits the best vaccine response against XBB.1.5,while recent infection can enhance this response.However, there is no significant advantage of the bivalent over the original vaccine in neutralizing XBB.1.5.Surbhi Gupta 1 , Francesco Borriello 2 , Jo-Chiao Wang 3 , Hannah Merrison 4 , Abigail J. Dutton 4 , David Dowling 2 , Clifford J. Woolf 2 , Ofer Levy 2 , Simmie Foster 4 , Sebastien Talbot 1,5 1 Queen's University, Kingston, ON; 2 Children's Hospital Boston, Boston, MA, USA; 3 University of Montreal, Montreal, QC; 4 Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; These findings suggest a role for nociceptors in maintaining humoral immunity after vaccination.We will further explore how sensory neuron ablation or overactivation affects B-cell trafficking and antibody production in response to vaccination and pathogen challenges in mice.This research provides insights into the role of nociceptor neurons in humoral immune responses during vaccination and has implications for the development of more effective vaccines.
Methods: 44 participants in a prospective cohort provided serum samples at 28-days post-third and fourth vaccine doses.IgG antispike, anti-RBD and neutralizing antibodies were measured against the Wuhan strain and XBB1.5.A multivariate mixed-effects model was employed to investigate the association between several predictors and covariates, including visit, vaccine type, recent infection, age, and sex, on ID50, a measure of neutralization efficiency.Linear regression within a multivariate mixed-effects framework was used to account5Karolinska Institutet, Solna, Sweden Correspondence: Surbhi Gupta Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):43 Background: Nociceptors, the sensory neurons that detect noxious stimuli and trigger pain, interact with immune cells to modulate immune responses.The nociceptor-released neuropeptide Substance P promotes B cell polarization, antibody class switching to IgE, and IgE release in models of allergic inflammation.In this study, we investigated whether nociceptors respond to vaccine adjuvants and control IgG production and clonal selection in the context of vaccination.Methods: We activated and sensitized sensory neurons from mice with vaccines and adjuvants against influenza virus and pneumococcal and meningococcal bacteria in vitro and evaluated influenza vaccinespecific IgG antibody levels in mice with ablated nociceptors.Results: Our results showed that sensory neurons respond to vaccines and exhibit differential activation by various noxious ligands.In mice with ablated nociceptors, IgG2c titers were reduced, while capsaicintreated mice showed increased IgG titers.Conclusions:

57 Anaphylaxis to leech bite: a case report with exploration of cross-sensitization and protein homologies
55 Recurrent pre-menstrual expression of contact hypersensitivity reactions in a woman sensitized to nickel Maggie Jiang, Peter Vadas Division of Allergy and Clinical Immunology, St. Michael's Hospital, University of Toronto, Toronto, ON Correspondence: Maggie Jiang Allergy, Asthma & Clinical Immunology 2024, 20(Suppl 1):55Background: It is recognized that women may be more prone to immediate hypersensitivity reactions in the few days leading up to the start of menses.This can occur with exposure to exogenous allergens (i.e., anaphylaxis to peanut during OIT) or endogenous allergens (i.e.catamenial anaphylaxis).Here, we report a case of cyclical contact hypersensitivity to nickel which recurs only pre-menstrually.from the sting reaction.She was started on medical management with a beta blocker and angiotensin receptor blocker (ARB).Conclusions: Allergic reactions can be associated with cardiac manifestations, for example Kounis syndrome.In this case, a stinging insect reaction was associated with Takotsubo cardiomyopathy.This case raises clinical dilemmas regarding the use of epinephrine autoinjectors and venom immunotherapy (VIT) in patients with cardiac sequelae and a previous epinephrine surge.

69 Food introduction in infant post-liver transplantation from deceased donor due to fatal anaphylaxis
We present a case of a 70-year-old man with hereditary angioedema diagnosed at age 18.He was treated with danazol 100 mg twice daily for greater than 20 years for long-term prophylaxis.His medical history was notable for renal transplant secondary to diabetic nephropathy on tacrolimus, mycophenolate, and prednisone.His history was negative for alcohol use and viral hepatitis.On a routine annual screening ultrasound, the patient was found to have a well-circumscribed mass to the liver.A biopsy confirmed hepatocellular carcinoma, later staged as pT1b.At the time of diagnosis, his liver enzymes were normal except for a mild elevation in ALP, and his Alpha-1-Fetoprotein was normal.He was managed with a surgical resection of the liver mass and cholecystectomy alone.The resected liver parenchyma was negative for cirrhosis on pathology.A CT scan performed one year later showed no evidence of residual tumor, and no new lesions.Once diagnosed with HCC, the patient was switched from danazol to lanadelumab.Conclusions: We report a case of HCC, a rare but serious toxicity from danazol in a patient with HAE.We hypothesize that concomitant immunosuppression in the setting of renal transplant may have increased his susceptibility to the development of HCC.Newer longterm prophylactic therapies with improved side effect profiles should be considered in patients with HAE.All participants/their guardians gave written and/or oral informed consent to participate and to be published.

of an inpatient penicillin allergy de-labelling program with direct oral challenge: a multicenter parallel cohort with crossover study
We conducted a one-week intensive allergy training course at the University of Rwanda which was integrated into the local curriculum.Seventeen senior medical residents in internal medicine, emergency medicine, otolaryngology, and dermatology attended.All materials were based on Canadian guidelines and modified for the Rwandan context, with instruction in English, supplemented by French and Kinyarwanda.Didactic lectures were given on immunodeficiency, allergic rhinitis, asthma, drug allergy, urticaria, food allergy, venom allergy and anaphylaxis.These were followed by objective structured clinical examinations and a final exam.Results: All residents were required to complete a survey to assess the effectiveness of this course.Overall, 16/17 (94%) of residents rated this course well (4-5/5), with main benefits being increased confidence in managing atopic conditions in their everyday practice.The main criticism was insufficient time allocation.Conclusions: Rwanda, like many other African nations, requires its own allergy and immunology program.Until then, our pilot teaching project can help fill the knowledge gap by instructing medical residents to recognize and treat anaphylaxis and other allergic conditions.Eventually, we hope that future Rwandan allergists can create their locally based and internationally standardized registries.Center for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia;10The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Parkville, VIC, Australia;11Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia;12Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia Patient 1, who reacted to gadobenate, had positive SPT and IDT to the latter with otherwise negative GBCA SPT/IDT and tolerated gadobutrol DPT.Patient 2, where gadobenate was implicated, had negative GBCA IDT and tolerated gadobutrol DPT.Patient 3, who reacted to gadoteridol, had a positive gadoteridol IDT.Gadobutrol IDT and DPT were negative.Patient 4, where gadoteridol was implicated, had positive IDT to gadoteridol and gadobutrol.Gadoxetate and gadobenate IDT were negative.Gadobenate DPT was tolerated.Patient 5, where gadoteridol was implicated, had negative IDT and DPT to gadoteridol.Patient 6, who reacted to gadobutrol, had negative gadobutrol IDT and DPT.Patients 7 and 8, where gadobutrol was implicated, had negative GBCA IDT.Upon gadobutrol and gadoteridol DPT respectively, they developed mild urticaria self-resolving in less than one hour, suggesting a non-IgE mediated reaction.Adhora Mir 1 , Derek Lanoue 2 , Carl van Walraven 1,3 , Timothy Olynych 1 , Veronica Zanichelli 3 , Caroline Nott 1,3 , Derek Macfadden1,3Methods: A retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses across two penicillin de-labelling intervention periods was conducted.Outcomes, including penicillin allergy labelling and antibiotic use, were collected for the index admission and the subsequent 6-month period.Descriptive statistics and multivariate regression analyses were performed.The penicillin allergy de-labelling intervention was associated with a reduction in penicillin allergy labels and increased utilization of beta-lactams in the subsequent 6-months.These results support the adoption of a proactive penicillin allergy de-labelling program to aid low-risk penicillin allergy de-labelling with direct oral challenge and support beta-lactam antibiotic use where indicated.
Conclusions:This study highlights the value of IDT with diverse GBCA, even after life-threatening IHR, to identify a tolerated GBCA.We propose a simple and safe 2-step DPT that can be easily implemented in clinical allergy practice.Introduction

84 Real-time monitoring of Fel d 1 concentrations during controlled cat allergen exposure in the SPaC-EEU
Fel d 1 concentrations across the four runs in the SPaC-EEU were not significantly different (mean: 51.58 ng/m 3 , 75.94 ng/m 3 , 53.99 ng/m 3 , 69.39 ng/m 3 ).Similar trends were observed between Fel d 1 concentrations from sampling cassettes and particle counts from the LPC in the runs when both were overlayed graphically.Fel d 1 concentrations were significantly and positively correlated (p < 0.05; r = 0.6071) with average particle counts at corresponding timepoints.Conclusions:The LPC can be used to indirectly monitor Fel d 1 concentrations in real-time during cat dander exposure in the SPaC-EEU.This enables greater control and consistency of dispersed allergen in the SPaC-EEU while ensuring participants' safety.

85 Clinical characteristics and management of food protein induced enterocolitis syndrome (FPIES) in Canadian children
Angela Mulé, Pasquale Mulé, Adnan Al Ali, Catherine Prattico, Xun Zhang, Christine McCusker, Moshe Ben-Shoshan Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC Correspondence

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The most common food triggers are egg and milk.The majority of reactions are not severe and baked goods containing the culprit food are often tolerated.Reference Background: The EMPOWER Study (NCT03845400) is a Phase IV observational, non-interventional, multicenter study evaluating realworld effectiveness and safety of lanadelumab in patients with HAE from Canada and US.We report outcomes in the Canadian patients from EMPOWER.Methods: Patients with HAE Type I/II could be enrolled in EMPOWER.This interim analysis included patients with ≥ 1 lanadelumab dose and ≥ 1 post-baseline effectiveness assessment who were new or prevalent (< 4 or ≥ 4 lanadelumab doses before enrollment, respectively) lanadelumab users.Results: As of March 1, 2022, 3/15 new and 2/87 prevalent lanadelumab users were from Canada.Mean ± SD age in new and prevalent Canadian users was 48.0 ± 10.2 and 62.5 ± 6.4 years, respectively, versus 40.6 ± 17.6 in EMPOWER overall.All Canadian patients were White, had HAE Type I, and most (66.7% new, 100% prevalent) were female, in agreement with EMPOWER overall (94.1% White, 76.5% HAE Type I, 65.7% female).Mean (95% CI) HAE attack rate in new Canadian users was 0.02 (0.01-0.03) attacks/month prelanadelumab and 0.03 (0.02-0.04) post-lanadelumab initiation; and 0.00 (0.00-0.00) in prevalent Canadian users during the study.In EMPOWER overall, mean (95% CI) attack rate in new users was 1.07 (0.93-1.23) attacks/month pre-lanadelumab and 0.22 (0.18-0.27) postlanadelumab initiation; and 0.16 (0.15-0.18) in prevalent users.The majority of HAE attacks in Canadian EMPOWER patients were mildto-moderate in severity, treated with plasma-derived C1 inhibitor, and did not require visits to healthcare professionals.There was 1 treatment-emergent adverse event (TEAE) in 1 new and 8 TEAEs in 1 prevalent Canadian user; all non-severe, non-serious, and not related to lanadelumab.Conclusions: In this interim analysis, Canadian patients from the real-world EMPOWER Study had higher age but otherwise similar demographic characteristics to overall EMPOWER population.Effectiveness and safety were consistent with interim results from EMPOWER overall.Remibrutinib is a novel, highly selective and potent, oral covalent BTKi with demonstrated efficacy, fast onset of action and favourable safety in CSU patients in a Phase 2b clinical study.We report the study design of REMIX-1(NCT05030311) and REMIX-2 (NCT05032157), two Phase 3 clinical trials, in CSU patients inadequately controlled by second-generation H1-antihistamines.Methods: REMIX-1 and REMIX-2 are multicenter, randomised, doubleblind, parallel-group, placebo-controlled, Phase 3 clinical trials conducted in parallel to evaluate the efficacy, safety, and tolerability of remibrutinib vs placebo in adult CSU patients.Studies consist of four periods, total duration of up to 60 weeks: Screening period (up to 4 weeks), double-blind treatment period (remibrutinib/placebo; 24 weeks), open-label treatment period (remibrutinib; 28 weeks) and treatment-free follow-up period (4 weeks).The studies include adult patients with CSU duration of ≥ 6 months, inadequately controlled (presence of itch and hives for ≥ 6 consecutive weeks and weekly Urticaria Activity Score [UAS7; range: 0-42] ≥ 16, weekly Itch Severity Score [ISS7; range: 0-21] ≥ 6 and weekly Hives Severity Score [HSS7; range 0-21] ≥ 6 during the 7 days prior to randomisation) by secondgeneration H1-antihistamines.Two primary objective scenarios will be tested independently: the first as primary endpoint of change from baseline in UAS7 at Week 12, and the second as co-primary endpoints of change from baseline in ISS7 and HSS7 at Week 12 (depending on regional precedent and Health Authority feedback).The study population will consist of approximately 450 patients (per trial) randomised in a 2:1 ratio to receive remibrutinib (n = 300) or placebo (n = 150).Results: The enrolment was initiated in Q4 2021 and the studies are expected to be completed in 2024.Conclusions: The results of the REMIX studies will provide further evidence to demonstrate the efficacy and safety of remibrutinib in CSU.